Delgado-Eckert Edgar, James Anna, Meier-Girard Delphine, Kupczyk Maciej, Andersson Lars I, Bossios Apostolos, Mikus Maria, Ono Junya, Izuhara Kenji, Middelveld Roelinde, Dahlén Barbro, Gaga Mina, Siafakas Nikos M, Papi Alberto, Beghe Bianca, Joos Guy, Rabe Klaus F, Sterk Peter J, Bel Elisabeth H, Johnston Sebastian L, Chanez Pascal, Gjomarkaj Mark, Howarth Peter H, Niżankowska-Mogilnicka Ewa, Dahlén Sven-Erik, Frey Urs
University of Basel, University Children's Hospital, Basel, Switzerland.
Center for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
J Allergy Clin Immunol. 2021 Aug;148(2):407-419. doi: 10.1016/j.jaci.2020.12.652. Epub 2021 Feb 3.
In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success.
We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics.
We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort.
Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin).
FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.
在所有慢性气道疾病中，气道功能的动态变化受潜在的气道炎症、支气管高反应性影响，同时由于气道和肺重塑以及黏液阻塞导致可逆性受限。各组成部分的相对作用转化为症状、生活质量、急性加重风险和治疗效果的特定临床模式。
我们旨在评估根据肺功能波动模式对阻塞性气道疾病患者进行亚组划分是否能识别出具有不同临床特征的特定表型。
我们将基于波动的聚类新方法（FBC）应用于欧洲BIOAIR队列中134名患有轻至中度哮喘、重度哮喘或慢性阻塞性肺疾病的成年混合组患者在1年期间每日两次记录的FEV测量值。
独立于临床诊断，FBC将患者分为4个基于波动的聚类，肺功能改变逐渐增加，这与临床严重程度增加、急性加重风险增加和生活质量降低的模式相对应。识别出气道疾病患者聚类，其与重塑相关的生物标志物（骨连接蛋白）和细胞衰老相关的生物标志物（纤溶酶原激活物抑制剂-1）水平显著升高，同时伴有气道可逆性丧失、肺过度充气和弥散能力丧失。所生成的4个聚类随时间稳定，且在2型炎症标志物（血液嗜酸性粒细胞和骨膜蛋白）水平上无差异。
基于FBC的表型分析提供了另一层次的信息，它与临床诊断互补且与嗜酸性粒细胞炎症无关，可识别可能从特定治疗策略或更密切监测中获益的患者。
